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TiCl₄-Promoted Intramolecular Friedel-Crafts Cyclization of α-Keto-phenylbutanoates: Synthesis of Substituted Indane

Arun K Ghosh¹, Tristan John McDonald¹

¹Department of Chemistry, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA.

Synlett : Accounts and Rapid Communications in Synthetic Organic Chemistry

|May 4, 2026

Abstract:

We report a TiCl₄-mediated intramolecular Friedel-Crafts type cyclization that provides convenient access to functionalized indane and indene derivatives. Reaction of α-ketoester derivatives bearing a phenylethyl side chain with 1.2 equiv of TiCl₄ in CH₂Cl₂ at -78 °C provided indanyl α-hydroxy ester in good yield. However, the reaction at - 78 °C to 23 °C furnished the corresponding elimination product, indene derivatives as a major product. Furthermore, the reaction of the keto ester with 1.2 equiv of TiCl₄ at -78 °C to 23 °C afforded an interesting dimeric indanyl-indane derivative in good yield. Presumably, the dimerization reaction proceeds via TiCl₄-mediated cationic intermediate.

Keywords:

Friedel-Crafts TiCl4 cationic reaction cyclization indene derivatives α-keto esters

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